Skip to main content
. 2000 Oct 31;97(23):12885–12890. doi: 10.1073/pnas.220412197

Table 1.

Dose-response relationship of neurotoxic action of 3NP in the rat striatum after systemic administration over 28 days and effect of the NMDA antagonists CPP, MK801, and memantine, and the AMPA/kainate antagonists NBQX and MPQX on 3NP toxicity

Treatment, mg/kg per d Striatal volume, mm3 Density of neurons in the striatum, NV; mean × 106/mm3 ± SEM Neurons, mean ± SEM % n
Vehicle 22.56  ± 0.93 0.141  ± 0.003 3,179,719  ± 148,757 100 13
3NP 12 + vehicle 23.05  ± 0.74 0.116  ± 0.004214 2,682,490  ± 144,728213 84 15
3NP 24 + vehicle 23.50  ± 0.61 0.057  ± 0.010219 1,301,823  ± 198,684219 41 8
3NP 12 + CPP 24 19.99  ± 0.75** 0.084  ± 0.006*** 1,665,659  ± 112,902*** 52 9
3NP 12 + MK801 0.3 20.33  ± 0.91* 0.088  ± 0.006*** 1,766,705  ± 114,380*** 56 6
3NP 12 + Memantine 24 20.42  ± 0.82* 0.086  ± 0.007*** 1,756,120  ± 115,768*** 55 9
Vehicle + CPP 24 22.35  ± 0.32 0.141  ± 0.005 3,156,938  ± 127,962 99 4
Vehicle + MK801 0.3 22.50  ± 0.63 0.141  ± 0.003 3,176,258  ± 99,183 100 6
Vehicle + Memantine 24 22.41  ± 0.41 0.140  ± 0.006 3,137,406  ± 135,672 99 4
3NP 12 + NBQX 24 22.61  ± 0.35 0.136  ± 0.004 3,080,253  ± 79,640* 97 6
3NP 24 + NBQX 24 22.95  ± 0.23 0.130  ± 0.009 3,000,500  ± 217,863$$$ 94 7
Vehicle + NBQX 24 22.63  ± 0.74 0.140  ± 0.004 3,175,564  ± 104,348 100 6
3NP 12 + MPQX 24 22.51  ± 0.32 0.135  ± 0.004 3,036,040  ± 60,090* 95 8
3NP 24 + MPQX 24 22.09  ± 0.39 0.121  ± 0.014 2,663,404  ± 277,681$$$ 84 6
Vehicle + MPQX 24 22.40  ± 0.30 0.141  ± 0.006 3,152,380  ± 125,392 99 8

Morphometric analyses revealed that striatal volume and Nv of striatal neurons were significantly reduced in rats subjected to parallel treatment with either 3NP, 12 mg/kg per d and CPP, or 3NP, 12 mg/kg per d and MK801, or 3NP, 12 mg/kg per d and memantine over 28 days. The total number of neurons lost in the striatum after combined treatment with 3NP and CPP, or 3NP and MK801, or 3NP and memantine was significantly higher than that in the striatum of rats subjected to 3NP and vehicle. NBQX and MPQX attenuated toxicity of 3NP decreasing loss of striatal volume and numerical density, and reducing loss of neurons in the striatum. The dose of either CPP, MK801, memantine, NBQX, or MPQX chosen for long-term treatment was the maximal tolerated dose that did not induce motor disturbances in rats.  

213

, P < 0.05;  

214

, P < 0.01;  

219

, P < 0.001 vs. vehicle-treated rats; *, P < 0.05; **, P < 0.01; ***, P < 0.001 vs. rats treated with 3NP, 12 mg/kg per d, and vehicle; $$$, P < 0.001 vs. rats treated with 3NP, 24 mg/kg per d, and vehicle (Student's t test).